Physical and functional plasticity appears to be a basic property of adult mammalian myocardium. The transition from normal to hypertrophied myocardium has been known for some time to occur rapidly in response to increased mechanical stress on the heart; this is a largely reversible process. Recently, I have shown that a transition from normal to atrophied myocardium occurs promptly in response to decreased mechanical stress. This markd cardiac plasticity in response to widely varying loading conditions demonstrates that the characteristic structure, composition and function of adult myocardium are not fixed properties, but are instead continuously modulated by a rather narrow range of normal hemodynamic loads. There are three specific aims of this application: first, to establish the mechanisms responsible for the regulation of myocardial structure, composition and function by both reduced and increased mechanical loads; second, to determine whether myocardial unloading results in dynamic, reversible changes or instead in fixed degenerationa; third, to utilize my model of unloaded myocardium to determine the relative imprortance of mechanical stress vs. sympathetic nerves in the induction and maintenance of cardiac hypertrophy. The first specific aim will be realized by measuring rates of protein synthesis and degradation as well as protein content in extirpated preparations of cat right ventricular myocardium subjected after isolation to normal, reduced or increased mechanical stress; myocardial ultrastructure and function will also be defined in these preparations. The second specific aim will be achieved by reloading in the intact heart a previously unloaded segment of cat right ventricular myocardium; the changes in structure, composition and function of this tissue over time will then be determined. The third specific aim will be approached by unloading a segment of cat right ventricular myocardium in two settings; either at the time that generalized right ventricular pressure overload hypertrophy is initiated or after this hypertrophy is fully developed; both unloaded and over loaded segments from these same ventricles will then be characterized as in the second specific aim over time. The long-term objective of the proposed research is to understand the importance of and the mechanisms for load regulation of the moycardium over the full potential spectrum of clinical loading conditions.